title: Cross-ethnic meta-analysis of genetic variants for polycystic ovary syndrome.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) have revealed new susceptibility loci for Chinese patients with polycystic ovary syndrome (PCOS). Because ethnic background adds to phenotypic diversities in PCOS, it seems plausible that genetic variants associated with PCOS act differently in various ethnic populations.
  
  
  OBJECTIVE
  We studied cross-ethnic effects of Chinese PCOS loci (ie, LHCGR, THADA, DENND1A, FSHR, c9orf3, YAP1, RAB5B/SUOX, HMGA2, TOX3, INSR, SUMO1P1) in patients of Northern European descent.
  
  
  METHODS
  This study was a genetic association study conducted at an University Medical Center.
  
  
  METHODS
  Association was studied in 703 Dutch PCOS patients and 2164 Dutch controls. To assess the cross-ethnic effect, we performed a meta-analysis of the Dutch data combined with results of previously published studies in PCOS patients from China (n = 2254) and the United States (n = 2618). Adjusted for multiple testing, a P value <3.1 × 10⁻³ was considered statistically significant.
  
  
  RESULTS
  Meta-analysis of the Chinese, US, and Dutch data resulted in 12 significant variants mapping to the YAP1 (P value = 1.0 × 10⁻⁹), RAB5B/SUOX (P value = 3.8 × 10⁻¹¹), LHCGR (P value = 4.1 × 10⁻⁴), THADA (P value = 2.2 × 10⁻⁴ and P value = 1.3 × 10⁻³), DENND1A (P value = 2.3 × 10⁻³ and P value = 2.5 × 10⁻³), FSHR (P value = 3.8 × 10⁻⁵ and P value = 3.6 × 10⁻⁴), c9orf3 (P value = 2.0 × 10⁻⁶ and P value = 9.2 × 10⁻⁶), SUMO1P1 (P value = 2.3 × 10⁻³) loci with odds ratios ranging from 1.19 to 1.45 and 0.79 to 0.87.
  
  
  CONCLUSIONS
  Overall, we observed for 12 of 17 genetic variants mapping to the Chinese PCOS loci similar effect size and identical direction in PCOS patients from Northern European ancestry, indicating a common genetic risk profile for PCOS across populations. Therefore, it is expected that large GWAS in PCOS patients from Northern European ancestry will partly identify similar loci as the GWAS in Chinese PCOS patients.
authors.affiliation: MD, Department of Gynecology and Obstetrics, Room Na-1524, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. y.louwers@erasmusmc.nl.
authors.forename: Yvonne V
authors.initials: YV
authors.lastname: Louwers
authors.forename: Lisette
authors.initials: L
authors.lastname: Stolk
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D009426:Netherlands; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors; D014481:United States; D000091102:YAP-Signaling Proteins; D020696:rab5 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; C503599:SUOX protein, human; D020696:rab5 GTP-Binding Proteins